The past and current theme of my research is the role viruses and virus-related genes play in the etiology of naturally occurring cancers. Within this framework our major approaches have included the population-level seroepidemiology, the immunobiology, and the virology of the agents involved. Until about 3 years ago most of our attention was directed to the study of the feline leukemia (FeLV) and feline sarcoma (FeSV) viruses in cats, since this represented the only outbred mammalian species where such studies could be conducted at both the population and individual host level. Recently we have devoted an increasing proportion of our laboratory effort to the study of human T-cell leukemia viruses (HTLV) and to hepatitis B virus (HBV). The studies with FeLV led to the first evidence that RNA tumor viruses are horizontally transmitted, the first evidence of retrovirus-induced immunosuppression, the identification of the first mammalian onc gene protein (in this case gag-fes) and the best evidence to date of immunosurveillance in a naturally occurring cancer. Studies with HBV led to evidence for replication in sites other than liver (lymphocytes). Studies with HTLV have let to identification of an HTLV agent as the apparent cause of AIDS, the first identification of the HTLV env gene products, the first demonstration of the pX putative transforming protein(s) of HTLV, and the link between HTLV-like agents and lymphoma development in monkeys. Hemophiliacs were shown to be infected with HTLV, and transfusion-associated AIDS were linked to HTLV exposure, using tests based on our observation that the env gene proteins are the most immunogenic for use as serologic markers. We plan to continue studying all 3 agents, as well as the newly identified primate virus, but with primary emphasis on the HTLV family. Our approaches will include studies on immunoregulation, and the characterization of viral and virus-induced proteins, both as markers for seroepidemiology and as keys to understanding leukemogenesis and lymphoid cell function. We will also study the role of HTLV-type agents in diseases such as aplastic anemia and AIDS. In the feline system our primary emphasis will be on mechanisms of FeLV-induced immunosuppression, and the role of FeLV and various onc genes in the causation of "virus-negative" cat tumors. With HBV we will continue to study the role of lymphoid and myeloid-stage infections and we will develop the monkey HTLV-related lymphoma and AIDS models to parallel our studies of HTLV in people.